RT Journal Article
SR Electronic
T1 Immuno-PET Imaging and Radioimmunotherapy of <sup>64</sup>Cu-/<sup>177</sup>Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1105
OP 1111
DO 10.2967/jnumed.115.167155
VO 57
IS 7
A1 Song, In Ho
A1 Lee, Tae Sup
A1 Park, Yong Serk
A1 Lee, Jin Sook
A1 Lee, Byung Chul
A1 Moon, Byung Seok
A1 An, Gwang Il
A1 Lee, Hae Won
A1 Kim, Kwang Il
A1 Lee, Yong Jin
A1 Kang, Joo Hyun
A1 Lim, Sang Moo
YR 2016
UL http://jnm.snmjournals.org/content/57/7/1105.abstract
AB Immuno-PET provides valuable information about tumor location, phenotype, susceptibility to therapy, and treatment response, especially to targeted radioimmunotherapy. In this study, we prepared antiepidermal growth factor receptor (EGFR) antibody via identical chelator, 3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-trience-3,6,9,-triacetic acid (PCTA), labeled with 64Cu or 177Lu to evaluate the EGFR expression levels using immuno-PET and the feasibility of radioimmunotherapy in an esophageal squamous cell carcinoma (ESCC) model. Methods: Cetuximab was conjugated with p-SCN-Bn-PCTA and radiolabeled with 64Cu or 177Lu. In vitro EGFR expression levels were determined and compared using flow cytometry and cell binding assay. In vivo EGFR expression levels were evaluated via immuno-PET imaging of 64Cu-cetuximab and biodistribution analysis. Micro-SPECT/CT imaging, biodistribution, and radioimmunotherapy studies of 177Lu-cetuximab were performed in the ESCC model. Therapeutic responses were monitored using 18F-FDG PET and immunohistochemical staining. Results: 64Cu- or 177Lu-labeled antibodies showed high radiolabeling yield (&gt;98%), stability (&gt;90%), and favorable immunoreactivity. In vitro EGFR status measured by cell binding assay was correlated with the flow cytometry data. Immuno-PET, micro-SPECT/CT, and biodistribution demonstrated specific uptake in ESCC tumors depending on the EGFR expression levels. Tumor accumulation of 64Cu- and 177Lu-cetuximab was peaked at 48 and 120 h, respectively. Radioimmunotherapy with 177Lu-cetuximab showed significant inhibition of tumor growth (P &lt; 0.01) and marked reduction of 18F-FDG SUV compared with that of control (P &lt; 0.05). Terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity and Ki-67 staining indices increased and decreased, respectively, in the radioimmunotherapy group compared with other groups (P &lt; 0.01). Conclusion: 64Cu-cetuximab immuno-PET represented EGFR expression levels in ESCC tumors, and 177Lu-cetuximab radioimmunotherapy effectively inhibited the tumor growth. The diagnostic and therapeutic convergence radiopharmaceutical 64Cu-/177Lu-PCTA-cetuximab may be useful as a diagnostic tool in patient selection and a potent radioimmunotherapy agent in EGFR-positive ESCC tumors.